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Sijaloreja i kserostomija u bolesnika s Parkinsonovom bolešću
Parkinson’s disease (PD) is generally considered as a primary movement disorder, but the majority of patients also suffer from non-motor oral, salivary symptoms. The most common salivary symptoms, sialorrhea and xerostomia, have a considerable negative impact on the quality of life. Although these symptoms are completely opposite ones, both significantly impair oral health of patients. Sialorrhea is defined as an increased amount of the retaining saliva. It is related to salivary overproduction, or it may be associated with impaired clearance of saliva. Opposed to sialorrhea, xerostomia is subjectively defined as dryness of mouth and it is related to insufficient salivary secretion. Xerostomia promotes imbalance of oral microflora and oral pathology that often leads to malnutrition in PD patients. It is mostly related to autonomic dysfunction, or it might be considered as a side effect of dopaminergic or anticholinergic medication. In PD, different assessments are used for evaluation of sialorrhea and xerostomia, including validated scales for non-motor symptoms and standardized questionnaires on oral health. Consequently, treatment of salivary symptoms includes pharmacological and nonpharmacological approach, and surgical interventions. A multidisciplinary approach in clinical neurology and dental medicine, which includes accurate evaluation of salivary symptoms and effective treatment, indicates successful management of PD patients.Parkinsonova bolest (PB) općenito se smatra primarnim poremećajem pokreta, ali većina bolesnika pati i od ne-motornih oralnih salivarnih simptoma. Najčešći salivarni simptomi, sijaloreja i serostomija, imaju značajan negativan utjecaj na kvalitetu života bolesnika. Iako su navedeni simptomi potpuno suprotni, oboje značajno narušavaju oralno zdravlje bolesnika. Sijaloreja se definira kao povećana količina zadržavajuće sline, a povezana je s prekomjernim lučenjem sline ili nedostatnim odstranjivanjem sline. Za razliku od sijaloreje, kserostomija se subjektivno definira kao suhoća usta i povezana je s nedovoljnim lučenjem sline. Kserostomija potiče neravnotežu oralne mikroflore i oralnu patologiju koja često dovodi do pothranjenosti kod bolesnika s PB. Povezana je s autonomnom disfunkcijom ili se može smatrati nuspojavom dopaminergičkih ili antikolinergičkih lijekova. U PB se za procjenu sijaloreje i kserostomije primjenjuju različite metode procjene, uključujući standardizirane ljestvice za procjenu ne-motoričkih simptoma i upitnike oralnog zdravlja. Slijedom toga, liječenje salivarnih simptoma uključuje farmakološki i ne-farmakološki pristup te kirurške intervencije. Multidisciplinarni pristup u kliničkoj neurologiji i dentalnoj medicini, koji obuhvaća preciznu procjenu salivarnih simptoma te učinkovito liječenje, ukazuje na uspješno liječenje bolesnika s PB
Tailoring functional spray-dried powder platform for efficient donepezil nose-to-brain delivery
Shortcomings of oral donepezil administration in the treatment of Alzheimer’s disease have paved the way for ongoing investigations towards more efficient and safe donepezil nose-to-brain delivery. Herein we present the development of advantageous powder platform for donepezil nose-to-brain delivery, coupling careful design of chitosan and mannitol-based carrier matrix with spray-drying technology advantages and early consideration of adequate nasal administration mode, employing QbD approach. Unprecedentedly, ultrasonic nozzle was used to atomise the drying feed in response to size-related requirements for nasal aerosol particles. The optimised spray drying process resulted in free-flowable dry powder with a great majority of particles larger than 10 µm, ensuring localised nasal deposition upon aerosolization, as evidenced by using 3D-printed nasal cavity model. QbD approach coupling formulation, process and administration parameters enabled optimisation of drug deposition profile reaching tremendously high 65.5 % of the applied dose deposited in the olfactory region. The leading formulation exhibited favourable swelling, mucoadhesion, drug release and permeation-enhancing properties, suiting the needs for efficient brain-targeted delivery. Results of in vitro biocompatibility and physico-chemical stability studies confirmed the leading formulation potential for safe and efficient donepezil nose-to-brain de livery. The obtained results encourage extending the study to an appropriate in vivo model needed for the final proof-of-concept
In situ gelling nanosuspension as an advanced platform for fluticasone propionate nasal delivery
In this work we present the development of in situ gelling nanosuspension as advanced form for fluticasone propionate nasal delivery. Drug nanocrystals were prepared by wet milling technique. Incorporation of drug nanocrystals into polymeric in situ gelling system with pectin and sodium hyaluronate as constitutive polymers was fine-tuned attaining appropriate formulation surface tension, viscosity and gelling ability. Drug nanonisation improved the release profile and enhanced formulation mucoadhesive properties. QbD approach combining formulation and administration parameters resulted in optimised nasal deposition profile, with 51.8% of the dose deposited in the middle meatus, the critical region in the treatment of rhinosinusitis and nasal polyposis. Results obtained in biocompatibility and physico-chemical stability studies confirmed the leading formulation potential for safe and efficient nasal corticosteroid delivery
Utjecaj neurotropnih virusa na preživljenje pacijenata operiranih od glioblastoma
Introduction: Glioblastoma represents the most aggressive tumor of the brain with an estimated survival rate of twelve to fifteen months after the primary diagnosis. The role of neurotropic viruses in pathogenesis of the tumor has remained unclear to date. During the last two decades, many studies were conducted with the aim of confirming viral influence in the development of glioblastoma.
Methods: We conducted a retrospective study in a time period of five years using formalin-fixed paraffin-embedded tissues of glioblastoma. Immunohistochemistry was performed for three viruses: CMV, EBV and HSV-1, using an automated staining system.
Results: Mean age of patients in our group was 66.7±8.5 years. A slight male dominance was noted. Negative immunohistochemistry results were obtained for CMV and EBV, which were excluded from further investigation. Based on IRS score, we confirmed six HSV-1 samples which were rated as IRS score 2. Five more samples of HSV-1 were rated as IRS score 1 and were excluded from the study.
Conclusion: According to our retrospective study and its results, we found no impact of neurotropic viruses in the survival rate of glioblastoma. Further studies should be conducted including a wider range of viral detection methods.Uvod: Glioblastom predstavlja najagresivniji tumor mozga s procijenjenom stopom preživljenja od dvanaest do petnaest mjeseci nakon primarne dijagnoze. Uloga neurotropnih virusa u patogenezi tumora do danas je nejasna. Tijekom posljednja dva desetljeća provedena su mnoga istraživanja s ciljem potvrde utjecaja virusa na razvoj glioblastoma.
Metode: Provedena je retrospektivna studija u vremenskom razdoblju od pet godina. Korištena su arhivska tkiva glioblastoma uklopljena u parafin. Imunohistokemija je rađena za tri virusa: CMV, EBV i HSV-1 pomoću automatiziranog sustava bojenja.
Rezultati: Prosječna dob bolesnika u našoj skupini bila je 66,7 ± 8,5 godina. Zabilježena je blaža predominacija oboljelih muškaraca. Dobiveni su negativni imunohistokemijski rezultati za CMV i EBV koji su isključeni iz daljnjeg ispitivanja. Prema IRS procjeni potvrdili smo šest uzoraka HSV-1 koji su ocijenjeni kao IRS 2. Još pet uzoraka HSV-1 ocijenjeno je kao IRS 1 i izuzeti su iz studije.
Zaključak: Prema našoj retrospektivnoj studiji i posljedičnim rezultatima, nismo pronašli utjecaj neurotropnih virusa na stopu preživljenja u oboljelih od glioblastoma, no potrebna su daljnja istraživanja koja uključuju širi spektar metoda dokazivanja virusa
Chronic multimorbidity of a low back disorder or other chronic back defects in the population of the European Health Interview Survey in the Republic of Croatia
To assess the prevalence of chronic multimorbidity in patients with a low back disorder or other chronic back defects (BD)
Global impact of the COVID-19 pandemic on subarachnoid haemorrhage hospitalisations, aneurysm treatment and in-hospital mortality: 1-year follow-up
Background: Prior studies indicated a decrease in the incidences of aneurysmal subarachnoid haemorrhage (aSAH) during the early stages of the COVID-19 pandemic. We evaluated differences in the incidence, severity of aSAH presentation, and ruptured aneurysm treatment modality during the first year of the COVID-19 pandemic compared with the preceding year.
Methods: We conducted a cross-sectional study including 49 countries and 187 centres. We recorded volumes for COVID-19 hospitalisations, aSAH hospitalisations, Hunt-Hess grade, coiling, clipping and aSAH in-hospital mortality. Diagnoses were identified by International Classification of Diseases, 10th Revision, codes or stroke databases from January 2019 to May 2021.
Results: Over the study period, there were 16 247 aSAH admissions, 344 491 COVID-19 admissions, 8300 ruptured aneurysm coiling and 4240 ruptured aneurysm clipping procedures. Declines were observed in aSAH admissions (−6.4% (95% CI −7.0% to −5.8%), p=0.0001) during the first year of the pandemic compared with the prior year, most pronounced in high-volume SAH and high-volume COVID-19 hospitals. There was a trend towards a decline in mild and moderate presentations of subarachnoid haemorrhage (SAH) (mild: −5% (95% CI −5.9% to –4.3%), p=0.06; moderate: −8.3% (95% CI −10.2% to –6.7%), p=0.06) but no difference in higher SAH severity. The ruptured aneurysm clipping rate remained unchanged (30.7% vs 31.2%, p=0.58), whereas ruptured aneurysm coiling increased (53.97% vs 56.5%, p=0.009). There was no difference in aSAH in-hospital mortality rate (19.1% vs 20.1%, p=0.12).
Conclusion: During the first year of the pandemic, there was a decrease in aSAH admissions volume, driven by a decrease in mild to moderate presentation of aSAH. There was an increase in the ruptured aneurysm coiling rate but neither change in the ruptured aneurysm clipping rate nor change in aSAH in-hospital mortality
Novel Clinical Insights into Spinal Hemangioblastoma in Adults: A Systematic Review
BACKGROUND: Hemangioblastomas (HBs) are well-vascularized, benign central nervous system tumors and the third most common primary spinal cord tumor after astrocytoma/ependymoma, occurring sporadically or as a part of autosomal dominant von Hippel-Lindau disease, in which tumors are often multiple and prone to relapse. Spinal HBs are commonly located in the cervical cord and associated with a syrinx formation. Owing to location and growth trends, they may cause significant neurological deficit, impairing quality of life. We conducted a systematic review to understand better clinical insights into spinal HB in adults and compare spinal HB versus posterior cranial fossa HB.
METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for conducting systematic reviews, we reviewed the English-language literature on adult spinal HB in the MEDLINE/PubMed database over the last 40 years.
RESULTS: We reviewed 237 articles on adult spinal HB and analyzed national and continental distribution, clinical symptoms, tumor location and presence of syringomyelia, treatment strategies and postoperative complications, histology and immunochemistry, and treatment outcomes. We compared individual characteristics in sporadic and von Hippel-Lindau disease spinal HBs. Finally, we compared features of posterior cranial fossa and spinal HBs.
CONCLUSIONS: Spinal cord HBs most commonly have a dorsal intramedullary location. Total surgical tumor resection is the first treatment option; preoperative embolization may be performed to reduce intraoperative bleeding and surgical time. HBs located in the spine have decreased mortality and rate of infection, but increased rates of cardiopulmonary complications compared with HBs in the posterior cranial fossa
Left Ventricular Ejection Fraction Can Predict Atrial Thrombosis Even in Non-High-Risk Individuals with Atrial Fibrillation
Background—Current guidelines do not recommend routine use of transesophageal echocardiography (TOE) in anticoagulated patients with atrial fibrillation (AF). The aim of our study was to identify predictors for left atrial thrombosis (LAT) in patients with AF that would require TOE despite anticoagulation therapy, using clinical, laboratory and echocardiographic data which are usually obtained in those patients in a real-world setting. Methods—We analyzed data from electronic medical records (EMR) of consecutive AF patients referred to two university hospitals between January 2014 and December 2017 for pulmonary vein isolation (PVI) or direct current cardioversion. The primary endpoint was the presence of left atrial thrombus on TOE. Multivariable and univariable logistic regression models were computed using variables that were significantly different between the LAT and the control groups. Results—A total of 838 patients were included, of whom 132 (15.8%) had LAT. After controlling for other variables, only the left ventricle ejection fraction (LVEF) remained statistically significant with an OR of 0.956 (95% CI 0.934–0.979), p < 0.01. Regression models including LVEF had significantly higher areas under the receiver operating characteristic (ROC) curves, including in subgroups with non-high thromboembolic risk (CHA2DS2-Vasc = 0 or 1), with an area under the curve (AUC) of 0.76 (95% CI 0.71–0.81), p < 0.0001. Conclusions—The LVEF is an independent predictor of LAT, and it might improve thromboembolic risk stratification in future models. LVEF significantly increased the predictive value of the CHA2DS2-Vasc model and was able to identify LAT in non-high-risk patients
Alpha satellite RNA levels are upregulated in the blood of patients with metastatic castration-resistant prostate cancer
The aberrant overexpression of alpha satellite DNA is characteristic of many human cancers including prostate cancer; however, it is not known whether the change in the alpha satellite RNA amount occurs in the peripheral tissues of cancer patients, such asblood. Here, we analyse the level of intracellular alpha satellite RNA in the whole blood of cancer prostate patients at different stages of disease and compare it with the levels found in healthy controls. Our results reveal a significantly increased level of intracellular alpha satellite RNA in the blood of metastatic cancers patients, particularly those with metastatic castration-resistant prostate cancer relative to controls. In the blood of patients with localised tumour, no significant change relative to the controls was detected. Our results show a link between prostate cancer pathogenesis and blood intracellular alpha satellite RNA levels. We discuss the possible mechanism which could lead to the increased level of blood intracellular alpha satellite RNA at a specific metastatic stage of prostate cancer. Additionally, we analyse the clinically accepted prostate cancer biomarker PSA in all samples and discuss the possibility that alpha satellite RNA can serve as a novel prostate cancer diagnostic blood biomarker